title: In vivo and in vitro liver and gill EROD activity in rainbow trout (Oncorhynchus mykiss) exposed to the beta-blocker propranolol.
abstract: The conservation of common physiological systems across vertebrate classes suggests the potential for certain pharmaceuticals, which have been detected in surface waters, to produce biological effects in nontarget vertebrates such as fish. However, previous studies assessing the effects of such compounds in fish have not taken into account the potential for metabolism and elimination. This study aimed to assess if propranolol, a β-adrenergic receptor antagonist or β-blocker, could modulate EROD activity (indicative of CYP1A activity) in rainbow trout (Oncorhynchus mykiss) gills and liver. For this, an in vivo time course exposure with 1 mg/L was conducted. Additionally, using measured in vivo plasma concentrations, an in vitro exposure at human therapeutic levels was undertaken. This allowed comparison of in vitro and in vivo rates of EROD activity, thus investigating the applicability of cell preparations as surrogates for whole animal enzyme activity analysis. In vitro exposure of suspended liver and gill cells at concentrations similar to in vivo levels resulted in EROD activity in both tissues, but with significantly higher rates (up to six times in vivo levels). These results show that propranolol exposure elevated EROD activity in the liver and gill of rainbow trout, and that this is demonstrable both in vivo (albeit nonsignificantly in the liver) and in vitro, thus supporting the use of the latter as a surrogate of the former. These data also provide an insight into the potential role of the gill as a site of metabolism of pharmaceuticals in trout, suggesting that propranolol (and feasibly other pharmaceuticals) may undergo "first pass" metabolism in this organ.
authors.affiliation: AstraZeneca, Safety Health and Environment, Brixham Environmental Laboratory, Freshwater Quarry, Brixham, Devon, TQ5 8BA, UK.
authors.forename: Abigail E
authors.initials: AE
authors.lastname: Bartram
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Winter
authors.forename: Duane B
authors.initials: DB
authors.lastname: Huggett
authors.forename: Paul
authors.initials: P
authors.lastname: McCormack
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Constantine
authors.forename: Malcolm J
authors.initials: MJ
authors.lastname: Hetheridge
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Hutchinson
authors.forename: Lewis B
authors.initials: LB
authors.lastname: Kinter
authors.forename: Jon F
authors.initials: JF
authors.lastname: Ericson
authors.forename: John P
authors.initials: JP
authors.lastname: Sumpter
authors.forename: Stewart F
authors.initials: SF
authors.lastname: Owen
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D019363:Cytochrome P-450 CYP1A1 / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D005880:Gills / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D022781:Hepatocytes / Q000187:drug effects / Q000201:enzymology; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D017686:Oncorhynchus mykiss / Q000378:metabolism*; D011433:Propranolol / Q000097:blood / Q000494:pharmacology*
chemical_list: D000319:Adrenergic beta-Antagonists; D011433:Propranolol; D019363:Cytochrome P-450 CYP1A1